Suicide risk in placebo-controlled trials of treatment for acute manic episode and prevention of manic-depressive episode

Objective: The authors' goal was to investigate whether there is a greater suicide risk in the placebo arms of placebo-controlled studies of active medication for the treatment of acute manic episode and the prevention of manic/depressive episode. If so, this would be a strong ethical argument against the conduct of such studies. Method: All placebo-controlled, double-blind, randomized trials of medication for the treatment of acute manic episode and the prevention of manic/depressive episode that were part of a registration dossier submitted to the regulatory authority of the Netherlands, the Medicines Evaluation Board, between 1997 and 2003, were reviewed for occurrence of suicide and attempted suicide. Results: In 11 placebo-controlled studies of the treatment of acute manic episode, including 1,506 patients ( 117 person-years) in the combined active compound group and 1,005 patients ( 71 person-years) in the combined placebo group, no suicides and no suicide attempts occurred. In four placebo-controlled studies of the prevention of manic/depressive episode, including 943 patients ( 406 person-years) in the combined active compound group and 418 patients ( 136 person-years) in the combined placebo group, two suicides (493/100,000 person-years of exposure) and eight suicide attempts ( 1,969/ 100,000 person-years of exposure) occurred in the combined active compound group, but no suicides and two suicide attempts ( 1,467/100,000 person-years of exposure) occurred in the combined placebo group. Conclusions: Concern about greater risk of suicide or attempted suicide in the placebo group should not be an argument against the conduct of placebo-controlled trials for these indications, provided that appropriate precautions are taken